Exploring the potential mechanism of emetine against coronavirus disease 2019 combined with lung adenocarcinoma: bioinformatics and molecular simulation analyses.
Adenocarcinoma of Lung
/ complications
Computational Biology
DNA-Binding Proteins
/ genetics
Emetine
/ pharmacology
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms
/ complications
Molecular Docking Simulation
SARS-CoV-2
/ drug effects
Serotonin Plasma Membrane Transport Proteins
/ genetics
Transcription Factors
/ genetics
COVID-19 Drug Treatment
Bioinformatics analyses
COVID-19
Emetine
Lung adenocarcinoma
Molecular docking
Molecular dynamics
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
22 Jun 2022
22 Jun 2022
Historique:
received:
27
01
2022
accepted:
08
06
2022
entrez:
22
6
2022
pubmed:
23
6
2022
medline:
25
6
2022
Statut:
epublish
Résumé
Patients with lung adenocarcinoma (LUAD) may be more predisposed to coronavirus disease 2019 (COVID-19) and have a poorer prognosis. Currently, there is still a lack of effective anti-LUAD/COVID-19 drugs. Thus, this study aimed to screen for an effective anti-LUAD/COVID-19 drug and explore the potential mechanisms. Firstly, we performed differentially expressed gene (DEG) analysis on LUAD transcriptome profiling data in The Cancer Genome Atlas (TCGA), where intersections with COVID-19-related genes were screened out. Then, we conducted Cox proportional hazards analyses on these LUAD/COVID-19 DEGs to construct a risk score. Next, LUAD/COVID-19 DEGs were uploaded on Connectivity Map to obtain drugs for anti-LUAD/COVID-19. Finally, we used network pharmacology, molecular docking, and molecular dynamics (MD) simulation to explore the drug's therapeutic targets and potential mechanisms for anti-LUAD/COVID-19. We identified 230 LUAD/COVID-19 DEGs and constructed a risk score containing 7 genes (BTK, CCL20, FURIN, LDHA, TRPA1, ZIC5, and SDK1) that could classify LUAD patients into two risk groups. Then, we screened emetine as an effective drug for anti-LUAD/COVID-19. Network pharmacology analyses identified 6 potential targets (IL6, DPP4, MIF, PRF1, SERPING1, and SLC6A4) for emetine in anti-LUAD/COVID-19. Molecular docking and MD simulation analyses showed that emetine exhibited excellent binding capacities to DDP4 and the main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study found that emetine may inhibit the entry and replication of SARS-CoV-2 and enhance tumor immunity by bounding to DDP4 and Mpro.
Sections du résumé
BACKGROUND
BACKGROUND
Patients with lung adenocarcinoma (LUAD) may be more predisposed to coronavirus disease 2019 (COVID-19) and have a poorer prognosis. Currently, there is still a lack of effective anti-LUAD/COVID-19 drugs. Thus, this study aimed to screen for an effective anti-LUAD/COVID-19 drug and explore the potential mechanisms.
METHODS
METHODS
Firstly, we performed differentially expressed gene (DEG) analysis on LUAD transcriptome profiling data in The Cancer Genome Atlas (TCGA), where intersections with COVID-19-related genes were screened out. Then, we conducted Cox proportional hazards analyses on these LUAD/COVID-19 DEGs to construct a risk score. Next, LUAD/COVID-19 DEGs were uploaded on Connectivity Map to obtain drugs for anti-LUAD/COVID-19. Finally, we used network pharmacology, molecular docking, and molecular dynamics (MD) simulation to explore the drug's therapeutic targets and potential mechanisms for anti-LUAD/COVID-19.
RESULTS
RESULTS
We identified 230 LUAD/COVID-19 DEGs and constructed a risk score containing 7 genes (BTK, CCL20, FURIN, LDHA, TRPA1, ZIC5, and SDK1) that could classify LUAD patients into two risk groups. Then, we screened emetine as an effective drug for anti-LUAD/COVID-19. Network pharmacology analyses identified 6 potential targets (IL6, DPP4, MIF, PRF1, SERPING1, and SLC6A4) for emetine in anti-LUAD/COVID-19. Molecular docking and MD simulation analyses showed that emetine exhibited excellent binding capacities to DDP4 and the main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
CONCLUSIONS
CONCLUSIONS
This study found that emetine may inhibit the entry and replication of SARS-CoV-2 and enhance tumor immunity by bounding to DDP4 and Mpro.
Identifiants
pubmed: 35733175
doi: 10.1186/s12885-022-09763-2
pii: 10.1186/s12885-022-09763-2
pmc: PMC9214478
doi:
Substances chimiques
DNA-Binding Proteins
0
SLC6A4 protein, human
0
Serotonin Plasma Membrane Transport Proteins
0
Transcription Factors
0
ZIC5 protein, human
0
Emetine
X8D5EPO80M
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
687Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2022. The Author(s).
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